The overall goal of this research is to determine the cellular mechanisms responsible for chemical oral irritation. This will be achieved by obtaining single unit recordings from rat lingual and chorda tympani nerves, and patch-clamp recordings from rat trigeminal ganglion neurons in response to chemical irritants. The irritants include those found in spices such as red and black pepper, horseradish, ginger, mustard, cinnamon, and onions; and in pollutants such as acids, alcohols, aldehydes, and acetates. When placed on lingual epithelium, these compounds produce a variety of sensations that range from warm to burning to painful. Emphasis will be placed on determining the neural responses elicited by capsaicin, the pungent ingredient in ed pepper that has been shown to activate a subset of pain fibers. Capsazepine, a specific capsaicin receptor antagonist, will be used to determine whether responses occur through capsaicin- sensitive pathways. Olvanil and tinyatoxin will be used as non-pungent capsaicin analogues. The specific aims include determining: 1) whether irritation is caused only by the activation of a subset of lingual nerve pain fibers, 2) whether irritants activate chorda tympani fibers, 3) whether activation of lingual nerve fibers is a consequence only of the irritants' activation of capsaicin receptors, 4) whether the irritant-induced currents in isolated trigeminal ganglion cells are inhibited by capsazepine, 5) whether a specific current is associated with pungency, and 6) whether irritants can modulate chorda tympani responses to taste stimuli. This research will provide fundamental information relating to taste, irritation, and pain. Regarding issues of health, capsaicin and its analogues are used clinically in relieving trigeminal neuralgia and vasomotor rhinitis as well as other painful symptoms. Understanding the basic mechanisms of how irritants activate nerves could lead to the development of effective countermeasures against irritating stimuli.